In the NIH-supported core projects conducted by the eight co-investigators of this proposal, Circular Dichroism (CD) spectropolarimetry provides a unique window into dynamic aspects of protein conformation and unfolding, conformational transitions accompanying peptide-membrane interaction and insertion, the development of less immunogenic, more effective therapeutic protein formulations, and the discovery of alternative formulations for poorly-soluble anticancer drugs. We seek to acquire a state-of-the-art CD spectropolarimeter to support and enhance these research programs. This instrument will provide convenient access to a well-supported but under-served group of investigators on one of three university campuses that are spread across this regional geographic area. Specific accessories on the instrument will make possible unique experimental approaches, such as programmed repetitive, simultaneous analysis of multiple samples, programmed thermal ramping studies to probe macromolecule conformation, acquisition of fluorescence emission data interleaved with CD measurements, and inclusion of an automated titrator for denaturation/refolding studies. These capabilities will enhance greatly the existing NIH-supported projects. The instrument will be operated by the Pharmaceutical Sciences Instrumentation Facility, which has operated successfully since 1995, when it brought the first shared-access CD instrument to the Western New York region. The facility has provided open access to users from the University at Buffalo (UB), our regional partners Roswell Park Cancer Inst. (RPCI) and Hauptman-Woodward Research Inst. (HWI), and occasional local college users. The current active user base is approximately 24 lab groups, the majority of which are NIH-funded. The facility also provides professional staff to train and assist new users, or perform collaborative work with less frequent users. Faculty associated with this facility and proposal also includes CD-related instruction in graduate-level courses, to provide graduate- and postdoctoral trainees with a sound basis of the theory and the potential applications of CD in their research projects.